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Quantitative analysis of peripheral tissue perfusion using spatiotemporal molecular dynamics.

Kang Y, Choi M, Lee J, Koh GY, Kwon K, Choi C - PLoS ONE (2009)

Bottom Line: Because near infrared (NIR) radiation can penetrate relatively deep into tissue, significant attention has been given to intravital NIR fluorescence imaging.Time-series NIR fluorescence images were obtained after injecting ICG intravenously in a murine hindlimb ischemia model.We propose that this novel NIR-imaging-based strategy is a powerful tool for biomedical studies related to the evaluation of therapeutic interventions directed at stimulating angiogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Bio and Brain Engineering, KAIST, Daejeon, Korea.

ABSTRACT

Background: Accurate measurement of peripheral tissue perfusion is challenging but necessary to diagnose peripheral vascular insufficiency. Because near infrared (NIR) radiation can penetrate relatively deep into tissue, significant attention has been given to intravital NIR fluorescence imaging.

Methodology/principal findings: We developed a new optical imaging-based strategy for quantitative measurement of peripheral tissue perfusion by time-series analysis of local pharmacokinetics of the NIR fluorophore, indocyanine green (ICG). Time-series NIR fluorescence images were obtained after injecting ICG intravenously in a murine hindlimb ischemia model. Mathematical modeling and computational simulations were used for translating time-series ICG images into quantitative pixel perfusion rates and a perfusion map. We could successfully predict the prognosis of ischemic hindlimbs based on the perfusion profiles obtained immediately after surgery, which were dependent on the preexisting collaterals. This method also reflected increases in perfusion and improvements in prognosis of ischemic hindlimbs induced by treatment with vascular endothelial growth factor and COMP-angiopoietin-1.

Conclusions/significance: We propose that this novel NIR-imaging-based strategy is a powerful tool for biomedical studies related to the evaluation of therapeutic interventions directed at stimulating angiogenesis.

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Related in: MedlinePlus

Quantitative measurement of perfusion rate based on spatiotemporal ICG dynamics.(A) Contrast NIR fluorescence angiography. (B) Temporal sequence of ICG fluorescence in the hindlimb ischemia model. The number indicates the time after ICG injection. (C) Temporal dynamics in the regions indicated with boxes in D are plotted. Relative fluorescence units (R.F.U.) were normalized to the maximal intensity. (D) Perfusion map reconstructed based on the time-series ICG images shown in B. (E) Histogram of perfusion rates in each limb for the regions indicated by the dotted box in D. The arrows indicate two perfusion rate peaks in the normal limb. (F) Photographic image of a normal hindlimb after skin excision to expose femoral vessels (right). Perfusion map of the limb (left). (H) Histogram of perfusion rates of the total hindlimb is indicated by the blue line, and the red line depicts the perfusion rates of the ROIs marked by the red line on femoral vessels.
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pone-0004275-g001: Quantitative measurement of perfusion rate based on spatiotemporal ICG dynamics.(A) Contrast NIR fluorescence angiography. (B) Temporal sequence of ICG fluorescence in the hindlimb ischemia model. The number indicates the time after ICG injection. (C) Temporal dynamics in the regions indicated with boxes in D are plotted. Relative fluorescence units (R.F.U.) were normalized to the maximal intensity. (D) Perfusion map reconstructed based on the time-series ICG images shown in B. (E) Histogram of perfusion rates in each limb for the regions indicated by the dotted box in D. The arrows indicate two perfusion rate peaks in the normal limb. (F) Photographic image of a normal hindlimb after skin excision to expose femoral vessels (right). Perfusion map of the limb (left). (H) Histogram of perfusion rates of the total hindlimb is indicated by the blue line, and the red line depicts the perfusion rates of the ROIs marked by the red line on femoral vessels.

Mentions: From equation 5, we could derive equation 6 and calculate the perfusion rate (P) of each pixel in the ROI using two parameters, the Tmax of each pixel and ICG half-life in the trunk. The simulation for the temporal ICG dynamics was run with different perfusion rate values (Figure S1B), which was consistent with actual ICG dynamics (see Figure 1C). The relationships among the ICG half-life, the time-to-peak, and the perfusion rate are shown in Figure S1C and D.


Quantitative analysis of peripheral tissue perfusion using spatiotemporal molecular dynamics.

Kang Y, Choi M, Lee J, Koh GY, Kwon K, Choi C - PLoS ONE (2009)

Quantitative measurement of perfusion rate based on spatiotemporal ICG dynamics.(A) Contrast NIR fluorescence angiography. (B) Temporal sequence of ICG fluorescence in the hindlimb ischemia model. The number indicates the time after ICG injection. (C) Temporal dynamics in the regions indicated with boxes in D are plotted. Relative fluorescence units (R.F.U.) were normalized to the maximal intensity. (D) Perfusion map reconstructed based on the time-series ICG images shown in B. (E) Histogram of perfusion rates in each limb for the regions indicated by the dotted box in D. The arrows indicate two perfusion rate peaks in the normal limb. (F) Photographic image of a normal hindlimb after skin excision to expose femoral vessels (right). Perfusion map of the limb (left). (H) Histogram of perfusion rates of the total hindlimb is indicated by the blue line, and the red line depicts the perfusion rates of the ROIs marked by the red line on femoral vessels.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2626246&req=5

pone-0004275-g001: Quantitative measurement of perfusion rate based on spatiotemporal ICG dynamics.(A) Contrast NIR fluorescence angiography. (B) Temporal sequence of ICG fluorescence in the hindlimb ischemia model. The number indicates the time after ICG injection. (C) Temporal dynamics in the regions indicated with boxes in D are plotted. Relative fluorescence units (R.F.U.) were normalized to the maximal intensity. (D) Perfusion map reconstructed based on the time-series ICG images shown in B. (E) Histogram of perfusion rates in each limb for the regions indicated by the dotted box in D. The arrows indicate two perfusion rate peaks in the normal limb. (F) Photographic image of a normal hindlimb after skin excision to expose femoral vessels (right). Perfusion map of the limb (left). (H) Histogram of perfusion rates of the total hindlimb is indicated by the blue line, and the red line depicts the perfusion rates of the ROIs marked by the red line on femoral vessels.
Mentions: From equation 5, we could derive equation 6 and calculate the perfusion rate (P) of each pixel in the ROI using two parameters, the Tmax of each pixel and ICG half-life in the trunk. The simulation for the temporal ICG dynamics was run with different perfusion rate values (Figure S1B), which was consistent with actual ICG dynamics (see Figure 1C). The relationships among the ICG half-life, the time-to-peak, and the perfusion rate are shown in Figure S1C and D.

Bottom Line: Because near infrared (NIR) radiation can penetrate relatively deep into tissue, significant attention has been given to intravital NIR fluorescence imaging.Time-series NIR fluorescence images were obtained after injecting ICG intravenously in a murine hindlimb ischemia model.We propose that this novel NIR-imaging-based strategy is a powerful tool for biomedical studies related to the evaluation of therapeutic interventions directed at stimulating angiogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Bio and Brain Engineering, KAIST, Daejeon, Korea.

ABSTRACT

Background: Accurate measurement of peripheral tissue perfusion is challenging but necessary to diagnose peripheral vascular insufficiency. Because near infrared (NIR) radiation can penetrate relatively deep into tissue, significant attention has been given to intravital NIR fluorescence imaging.

Methodology/principal findings: We developed a new optical imaging-based strategy for quantitative measurement of peripheral tissue perfusion by time-series analysis of local pharmacokinetics of the NIR fluorophore, indocyanine green (ICG). Time-series NIR fluorescence images were obtained after injecting ICG intravenously in a murine hindlimb ischemia model. Mathematical modeling and computational simulations were used for translating time-series ICG images into quantitative pixel perfusion rates and a perfusion map. We could successfully predict the prognosis of ischemic hindlimbs based on the perfusion profiles obtained immediately after surgery, which were dependent on the preexisting collaterals. This method also reflected increases in perfusion and improvements in prognosis of ischemic hindlimbs induced by treatment with vascular endothelial growth factor and COMP-angiopoietin-1.

Conclusions/significance: We propose that this novel NIR-imaging-based strategy is a powerful tool for biomedical studies related to the evaluation of therapeutic interventions directed at stimulating angiogenesis.

Show MeSH
Related in: MedlinePlus